The present invention is related to identifying landmarks which assist in visualizing internal structures during diagnostic and/or therapeutic procedures, including medical procedures.
Targeting aids or landmarking devices have been employed in diagnostic imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI)and ultrasound. These devices, commonly referred to as fiducial markers, generally occur as two types: internally occurring markers which are inherent in the subject""s anatomy; and externally positionable imaging aids which can be permanently or temporarily affixed to the body under analysis. External fiducial markers have also been proposed for use and used in other imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT)as well as in imaging techniques such as MRI and CT. No effective internally positionable devices have been developed.
Imaging techniques such as PET and SPECT rely upon cellular uptake of suitable imaging solutions such as 2-(18F)-fluoro-2-deoxy-D-glucose (FDG) to provide accurate images of metabolically active tissue, including cancerous or abnormal tissue material. Malignant cells such as those found in cancerous tumor tissue, generally exhibit elevated energy requirements resulting in elevated levels of glucose consumption. By comparison, surrounding tissue is less metabolically active. Imaging techniques such as PET make use of this differential in cellular glucose uptake by employing radiopharmaceutically tagged uptake solutions to demonstrate areas of interest for imaging and analysis. Other PET techniques such as image amino acid transport, DNA synthesis, etc., as well as SPECT can, for example, image overexpression of receptors on tumors. While both methods allow distinction of tumor from normal tissues, there are instances in which PET and SPECT are difficult to use as a single scanning modality.
One drawback of such radiopharmaceutically assisted imaging techniques is that the visualized area of increased tracer accumulation is best localized in comparison to known anatomical references in order to be precisely characterized and located in the subject""s body. In order to be visualized in a PET or SPECT scan, the anatomical element of interest must also be capable of sufficient uptake of radioactivity to provide a detectable emission. Thus, localization can be accomplished using PET or SPECT when a known anatomical landmark also exhibits increased radiotracer uptake relative to the surrounding imaged tissues. In such instances, the landmark can provide a reference against which the region under study can be located, analyzed and measured. This requirement becomes problematic in regions of greater anatomical variation, and in regions which have little radiotracer uptake on scan. Such regions provide few reference landmarks which have levels of increased cellular glucose or other tracer uptake.
This problem becomes more pronounced in situations where imaging data generated from PET or SPECT scans are to be integrated with imaging data derived from other methods such as,,i.e., MRI, CT, or ultrasound. As described in Wahl et al., xe2x80x9cAnatometabolic Tumor Imaging: Fusion of FDG PET with CT or MRI to Localize Foci of Increased Activity,xe2x80x9d J. Nucl. Med; 34(7); 1190-1197, (1993) xe2x80x9cmetabolicxe2x80x9d data generated from PET studies of specific anatomical regions have been fused with imaging data generated by MRI and/or CT to visualize xe2x80x9chot spotsxe2x80x9d generated by abnormal cellular activity. Such data have been registered to anatomical images generated by MRI and/or CT. In Thornton et al., xe2x80x9cA Head Immobilization System for Radiation Simulation, CT, MRI, and PET Imaging,xe2x80x9d Medical Dosimetry; 16; 51-56, (1991), contour tubing is permanently mounted to immobilizing masks used in simulation planning and during radiation treatment for both central nervous system and cranial and facial tumors. A suitable positron emission material such as a fluorine-18 solution is inserted in the tubes to provide a positron emission from the known external source. The authors describe an external marker system that provides a reference system for imaging correlation.
In the process described in the Wahl et al. reference, external fiducial markers were placed during both anatomic (CT and MRI) and metabolic (PET) studies. These external fiducial markers, as well as inherent internal anatomical landmarks were used to reconstruct fused images from the various imaging studies. This permitted greater accuracy in localizing of structures of interest.
U.S. Pat. No. 4,884,566 to Mountz et al. is directed to an externally positioned apparatus for defining a plane of an image through a portion of the body. The device includes a frame onto which a plurality of channels can be mounted. A suitable imaging material can be contained in the channels to provide reference markers during scanning.
The methods and devices described in the Wahl and Thornton references present difficulties when employed to visualize regions where greater patient-to-patient anatomical variation is encountered. Such regions often lack internal landmarks or accurate correlation with the positioning of external fiducial markers. The device disclosed in Mountz has an effective use in imaging more confined and rigid regions like the cranium. However, external devices such as the Mountz device or that disclosed in Thornton are not designed for marking internal imaging regions such as the chest, abdomen or pelvis. In addition, external markers do not localize deep anatomy.
In three-dimensional radiation treatment planning, the ability to visualize targets and critical structures is crucial. These critical structures are organs which receive radiation dose but are not themselves targets for treatment. Examples of critical structures include, but are not limited to the optic chasm, esophagus, spinal cord, small and large bowels, rectum, kidneys, vaginal walls, etc. Knowledge of the location of critical structures, as well as the targeted tissue for treatment, permits more accurate targeting and precise administration of radiation dose and greater sparing of normal tissue radiation toxicity.
The problem can present in many situations, for example, when functional imaging is introduced into radiation treatment planning for thoracic cancers such as lung cancer. In such situations it is important to visualize critical structures such as the esophagus in a manner which will permit the radiation oncologist to locate and identify critical structures and to locate the target tissue to plan and administer therapeutic radiation dose in the most precise and accurate manner possible. Critical structures such as esophageal tissue are difficult to visualize in PET due to relatively low metabolic uptake of radiopharmaceutical marker by the esophagus, particularly in relation to the target tumor. Under such circumstances, metabolic emission imaging techniques such as PET or SPECT are of limited efficacy.
References such as Wahl et al. have proposed fusing data produced from metabolic imaging techniques with data generated from other imaging techniques. However, accurate visualization of certain critical structures or targets can be difficult even in multiple imaging systems. MRI is particularly sensitive to moving tissue. Even a reproducibly stationary-positioned patient will produce motion from breathing, heart rate or peristalsis which can create image displacement or edge blurring artifacts. MRI motion artifact correction techniques such as retrospective triggering and respiratory compensation as well as gradient motion compensation do not completely remove motion artifacts from an MRI image, (Brown et al. xe2x80x9cMRI Imaging, Abbreviations, Definitions and Descriptions: A Review,xe2x80x9d Radioloay (1999) 213(3): 647.) Deep anatomy fiducial markers can facilitate inclusion of MRI imaging in multi-imaging modality fusion by complementing existing MRI artifact correction techniques.
The sensitivity and specificity of ultrasound is limited when applied to the study of small and deep anatomic structures. The utility of ultrasound imaging for multimodality image fusion would be enhanced through the use of an internal fiducial marker containing contrast agents that produce a homogeneous transmission of sound, harmonics or echogenicity. When targets and critical structures can be visualized by imaging techniques such as but not limited to PET, SPECT, MRI, ultrasound, CT or mammography, the ability to obtain fused multi-imaging data is limited, due, in part, to the absence of effective constant landmarks such as internal fiducial markers.
Based on the limitations of the imaging modalities described above, it is desirable to have means for more accurately identifying internal critical structures in various imaging techniques. It is also desirable to provide utility for maximum use of existing techniques for demonstrating morphologic and molecular disease. This is one of the research priorities of the United States National Cancer Institute.
In one aspect, the present invention is directed to a device for visualizing structure located in the interior of a substance which is visually opaque. As used herein, the term xe2x80x9cvisually opaquexe2x80x9d is taken to mean obscure or unapparent using characteristic imaging modalities. The present invention provides a method and apparatus based on removably positionable internal fiducial markers as a targeting aid or a landmarking or verification device for various imaging techniques. The device is capable of being removably inserted into a suitable lumen or cavity in the subject to be scanned or imaged. The device contains a material detectable by imaging techniques, and such material is capable of emitting a detectable reference signal relative to the focus of the imaging scan. More particularly, the device, which is removably inserted into a subject and emits a detectable signal by one or more imaging modalities, assists in visualizing an internal organ structure, and assists in the positioning, localization and imaging of tissue or cell clusters of interest within a visual field which encompasses the removably positionable device and the tissue of interest during scanning or imaging procedures.
The device of the present invention includes at least removably insertable marker member which, when in place in the desired region of the body to be imaged will act as a suitable fiducial marker for the type of scan or scans to be performed. The removably insertable marker member may be a solid member or may have a suitably configured void space located therein. This void space may be either a hollow cavity defined in one region of the marker member or it may be a hollow conduit running at least partially though the length of the marker member such as a lumen. The body of the marker member may be either flexible or suitably rigid, depending on the nature of the anatomical structure to be visualized.
The marker member has a proximal end, and a distal end. The distal end of the marker member is removably insertable in the visually opaque substance relative to the internal structure to be visualized. The body of the marker member is composed of a biologically stable substrate material. As used herein, the term xe2x80x9cbiologically stable substratexe2x80x9d is a material which will remain essentially non-interactive with the visually opaque substance to be visualized or the system or organism in which the opaque substance is contained. The biologically stable substrate material may be one which can produce an MRI, positron or ultrasound signal. Preferably at least one imaging material is contained in the lumen in a manner which prevents the imaging material from direct contact with surrounding visually opaque substance. The imaging material of choice is one which is capable of producing an emission detectable external to the visually opaque substance. It is also within the scope of this invention that the solid substrate material may be one which can produce an MRI, Positron or ultrasonic signal. The visually opaque substance is, preferably, a biological substance and, most preferably, an anatomical structure as would be found in a human or other mammal. The imaging material may be a substance which is capable of magnetic resonance, visually dense under ultrasonic or x-ray scanning or capable of emitting a detectable emission such as a radiopharmaceutical imaging material.
The entire apparatus or portions thereof may produce the relevant signal for imaging. That is to say that the marker member can be a solid which is composed, at least in part, of a material suitable for use in the imaging modalities enumerated previously. This solid may be imaging material itself or may be a solid which may suitably contain the desired imaging material through at least a portion of the body of the device. The imaging material, when contained on a portion or segment of the body of the marker member, may be positioned on a discrete region or regions. The positioning of the imaging material positioning may be transverse on the body of the device or may be located on discrete longitudinal region or regions depending on the requirements of the imaging procedure.
In an alternative, the marker member may be composed of at least one lumen. The lumen may be suitably flexible, partially flexible or possess the degree of rigidity desired or required by the particular tissue or anatomical region under analysis.
The present invention is also directed to a process for visualizing difficult-to-visualize critical structures through a method which employs the removable device of the present invention. In the contemplated method, the removable device of the present invention is inserted into position in the interior of a physical cavity integral in the visually opaque substance. Emissions generated from the imaging material or changed sonographic or magnetic resonance signal characteristics resulting from the imaging material contained in the device of the present invention are recorded and localized. Any emission signal generated from any other regions of the visually opaque material are also recorded and localized. Emission signals recorded and localized are integrated into translatable data. After the data has been obtained, the visualizing device and all imaging source material contained therein are removed from the interior of the visually opaque substance.